In conventional DNA synthesis methods, the introduction of a 3′-end nucleoside unit on a solid-phase support was done by the formation of amide bond with an amino group on the solid-phase support using a linker such as a succinate linker or silyl linkers for the 3′-end nucleoside.
For example, a benzoic acid-type compound: iP2Si—C6H4—C(O)-type that was developed by one of the present inventors, SEKINE Mitsuo, is known as a silyl linker that can be cut out under a neutral condition (Non-Patent Document 1). However, since such silyl linker will be introduced into amino groups on the solid-phase support by acylation, the amino groups contained in dA, dC and dG have to be protected in advance with an appropriate protecting group such as DMTr.
Furthermore, as the DMTr protecting group in the base moiety of dC is relatively stable, treatment with 5% trifluoroacetic acid-CH2Cl2 solution for 30 min would be required to completely remove said protecting group. However, SiO bonds contained in the silyl linker and those formed between the silyl linker and a synthesized DNA oligomer would likely be cleaved under such a very acidic condition as in the above treatment.
Non-Patent Document 1: Wada, T.; Mochizuki, A.; Sato, T.; Seike, M.; M., Tetrahedron Letters, 1998, 39, 5593-5596